Update: HPV vaccine offers cross-protection
Good news: Recent research indicates that the human papillomavirus (HPV) vaccine Gardasil (Merck & Co.; Whitehouse Station, NJ) also provides about 40% cross-protection against other common oncogenic strains of HPV, in addition to its established strains.1
"Based on the data presented at the Interscience Conference on Antimicrobial Agents and Chemotherapy, we expect that women vaccinated with Gardasil will benefit from an additional degree of protection against cancer-causing HPV types other than HPV 16 and 18," says Darron Brown, MD, professor of medicine, microbiology, and immunology at the Indiana University School of Medicine in Indianapolis, who presented the study results. "The next step is to educate families and young women on the benefits of Gardasil in protecting against cervical cancer and other genital tract cancers."
The research, an analysis of two large Phase III clinical trials of the vaccine, found that Gardasil showed cross-protection against precancerous lesions caused by an additional 10 HPV strains: 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59. The 10 HPV strains, which are members of the A9 and A7 species, are responsible for more than 20% of all cervical cancers worldwide and a large proportion of high- and low-grade cervical lesions.2,3
The clinical trials involved administering three doses of Gardasil or a placebo to females ages 15-26. Participants also underwent cervical-vaginal sampling and Pap tests at the beginning of the study and at six- to 12-month intervals for up to 48 months.
Merck is working with partners in the international community to develop sustainable solutions to bring Gardasil to the developing world. The company has announced that it will donate at least 3 million doses of Gardasil to developing countries. Gardasil was launched in the United States in June 2006 and in Europe in September 2006.
Another vaccine on the way?
Providers may see another HPV vaccine in 2008 if the Food and Drug Administration (FDA) gives approval to Cervarix, a HPV vaccine candidate from GlaxoSmithKline USA of Philadelphia. The Biologics License Application for the vaccine is being reviewed by the FDA under a 10-month review period, says Liad Diamond, a company spokeswoman. The application was submitted in late March 2007, and the company expects to hear from the FDA in early 2008, she states.
The European Commission approved Cervarix for sale and marketing in the European Union in September 2007. Cervarix already is available in Australia; the vaccine came online in that country last May.
Cervarix and Gardasil are being studied in a head-to-head comparison. The trial is designed to compare the immune responses to HPV types 16 and 18 in U.S. women ages 18-26, as well as evaluate the immune responses to HPV 16 and 18 in women ages 27-35 and 36-45. In addition, the study will compare immune responses to other cancer-causing HPV types.
What's the next step?
What about an HPV vaccine for men? Merck is sponsoring a clinical trial of Gardasil in 4,000 men, including 500 self-identified gay men. Initial results are expected toward the end of 2008.4
The trial includes a heterosexual male cohort evaluating the efficacy of the quadrivalent vaccine for preventing genital warts and a gay male cohort in evaluating the efficacy of the quadrivalent vaccine in preventing anal carcinoma. With no data yet available, the Gardasil vaccine is not currently recommended for men.
How about use of the vaccine in older women? Merck is conducting Gardasil clinical trials in women as old as 45, but results are not yet available. Research released earlier in 2007 indicates that at 18 months after the first of a three-dose regimen, 100% of women up to age 55 vaccinated with the candidate vaccine had antibodies present against the two most common cancer-causing HPV types, 16 and 18.5
"Women are not infected with HPV by breathing in infected air or drinking infected water, " notes Robert Hatcher, MD, MPH, professor of gynecology and obstetrics at Emory University School of Medicine in Atlanta. "They are usually infected by sexual intimacy with a man, and a vaccine for men is of paramount importance."
- Brown D. The Future Study Group. HPV Type 6/11/16/18 vaccine: First analysis of cross-protection against persistent infection, cervical intraepithelial neoplasia (CIN), and adenocarcinoma in situ (AIS) caused by oncogenic HPV types in addition to 16/18. Presented at the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy. Chicago; September 2007. Abstract G-1720b.
- Clifford GM, Smith JS, Aguado T, et al. Comparison of HPV type distribution in high-grade cervical lesions and cervical cancer: A meta-analysis. Br J Cancer 2003; 89:101-105.
- Clifford GM, Rana RK, Franceschi S, et al. Human papillomavirus genotype distribution in low-grade cervical lesions: Comparison by geographic region and with cervical cancer. Cancer Epidemiol Biomarkers Prev 2005; 14:1,157-1,164.
- Tuller D. New vaccine for cervical cancer could prove useful in men, too. The New York Times, Jan. 20, 2007; accessed at query.nytimes.com.
- Schwarz TF, Dubin G. HPV Vaccine Study Investigators for Adult Women. Human papillomavirus (HPV) 16/18 l1 AS04 virus-like particle (VLP) cervical cancer vaccine is immunogenic and well-tolerated 18 months after vaccination in women up to age 55 years. J Clin Oncol 2007; 25:18s.